Doxepin hydrochloride is a tricyclic compound most frequently used to treat the affective disorders depression and anxiety, but also less commonly employed as a secondary or tertiary treatment modality for a variety of painful (e.g. headache and neuropathic pain) and allergic (e.g. urticaria) disorders. While doxepin is generally recognized as effective for the treatment of such disorders, its use is limited by the systemic side effects associated with its ingestion or topical application. Principal among the systemic side effects accompanying doxepin administration, and most limiting to its usefulness as a drug, is sedation which occurs in from 20% to over 60% of subjects depending upon dosage and route of doxepin administration. According to USP 25,2000. United States Pharmacopeial Convention, Inc., Rockville, Md. p. 614, doxepin hydrochloride U.S.P. is a geometric isomer mixture “containing not less than 13.6% and not more than 18.1%” of this cis isomer and “not less than 81.4% and not more than 88.2%” of the trans isomer.
In an attempt to discover a compound that might have similar effectiveness to doxepin hydrochloride U.S.P. but less associated sedation, the applicant has evaluated the cis isomer, which as mentioned above constitutes less than 18.1% of doxepin hydrochloride. Applicant has discovered that cis doxepin hydrochloride, while purportedly more potent than doxepin hydrochloride U.S.P. in animals, quite surprisingly produces substantially less sedation at therapeutically effective dosages. The invention includes pharmaceutical compositions of cis doxepin suitable for administration to patients with affective disorders, painful disorders, or allergic disorders.